Aggiornamento
Aftosi orale ricorrente: una, nessuna, centomila
RECURRENT APHTHOUS STOMATITIS
GIANLUCA TORNESE, INES L’ERARIO, LOREDANA LEPORE, GIOVANNA VENTURA, FEDERICO MARCHETTI, ALESSANDRO VENTURA
Clinica Pediatrica, IRCCS “Burlo Garofolo”, Università di Trieste
Maggio 2008 - pagg. 291 -299
Abstract
Recurrent aphthous stomatitis (RAS) (also referred as aphthae or canker sores) is a common
disorder affecting up to 60-70% of the general population at any time. Usually, RAS is a
well-defined clinical condition (recurrent painful ulcers confined to the mouth, in the absence
of systemic disease, with spontaneous resolution in few days) and as a rule it is easily recognized
(and accepted as paraphysiological) by the patient. Nevertheless, other
aphthous lesions may resemble but are different from RAS. Additional clinical signs (i.e. fever)
should be valued since they lead to exclude RAS by definition and impose to suspect
some other disorders. This article proposes a review of the etiopathogenesis, differential diagnosis and management of RAS in primary care.
Classificazione MeSH
Bibliografia
1. Scully C, Gorsky M, Lozada-Nur F. The diagnosis
and management of recurrent aphthous
stomatitis: a consensus approach. J Am
Dent Assoc 2003;134:200-7.
2. Porter SR, Scully C, Pedersen A. Recurrent aphthous stomatitis. Crit Rev Oral Biol Med 1998;9(3):306-21.
3. Scully C. Aphthous ulceration. N Engl J Med 2006;355:165-72.
4. Natah SS, Konttinen YT, Enattah NS, Ashammakhi N, Sharkey KA, Häyrinen-Immonen R. Recurrent aphthous ulcers today: a review of the growing knowledge. Int J Oral Maxillofac Surg 2004;33:221-34.
5. Rogers RS 3rd. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg 1997;16:278-83.
6. Cooke BED. Recurrent oral ulcers. Br J Dermatol 1969;81:159-61.
7. Lehner T. Autoimmunity in oral diseases, with special reference to recurrent oral ulceration. Proc R Soc Med 1968;61:515-24.
8. Pedersen A. Recurrent aphthous ulceration: Virological and immunological aspects. APMIS 1993;101(Suppl 37):37.
9. Martin DK, Nelms DC, Macler BF, Peavy DL. Lymphoproliferative responses induced by streptococcal antigens in recurrent aphthous stomatitis and Behçet’s syndrome. Clin Immunol Immunopathol 1979;13:1446-55.
10. Lindemann RA, Riviere GR, Sapp JP. Serum antibody responses to indigenous oral mucosal antigens and selected laboratorymaintained bacteria in recurrent aphthous ulceration. Oral Surg 1985;59:585-9.
11. Eglin RP, Lehner T, Subak-Sharpe JH. Detection of RNA complimentary to herpes simplex virus in mononuclear cells from patients with Behçet’s syndrome and recurrent oral ulcers. Lancet 1982;2:1356-61.
12. Studd M, McCance DJ, Lehner T. Detection of HSV-1 DNA in patients with Behçet’s syndrome and in patients with recurrent oral ulcers by the polymerase chain reaction. J Med Microbiol 1991;34:39-43.
13. Ship II. Epidemiologic aspects of recurrent aphthous ulcerations. Oral Surg Oral Med Oral Pathol 1972;33:400-6.
14. Miller MF, Ship II. A retrospective study of the prevalence and incidence of recurrent aphthous ulcers in a professional population, 1958-1971. Oral Surg Oral Med Oral Pathol 1977;43:532-7.
15. Ferguson MM, Wray D, Carmichael HA, Russell RI, Lee FD. Coeliac disease associated with recurrent aphthae. Gut 1980;21:223-6.
16. Freysdottir J, Lau S, Fortune F. Gammadelta T cells in Behçet’s disease (BD) and recurrent aphthous stomatitis (RAS). Clin Exp Immunol 1999;118:451-7.
17. Natah SS, Hayrinen-Immonen R, Hietanen J, Malmstrom M, Konttinen YT. Immunolocalization of tumor necrosis factor-alpha expressing cells in recurrent aphthous ulcer lesions (RAU). J Oral Pathol Med 2000;29(1):19-25.
18. Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med 1991; 173:699-703.
19. Pizarro A, Herranz P, de Lucas R, Borbujo J, Casado M. Pentoxifylline in recurrent aphthous stomatitis. J Am Acad Dermatol 1997; 36(2 Pt 1):284.
20. Sfikakis PP. Behçet’s disease: a new target for anti-tumour necrosis factor treatment. Ann Rheum Dis 2002 Nov;61 (Suppl 2):ii51-3.
21. Lewkowicz N, Lewkowicz P, Banasik M, Kurnatowska A, Tchorzewski H. Predominance of Type 1 cytokines and decreased number of CD4(+)CD25(+high) T regulatory cells in peripheral blood of patients with recurrent aphthous ulcerations. Immunol Lett 2005;99:57-62.
22. Buno IJ, Huff JC, Weston WL, Cook DT, Brice SL. Elevated levels of interferon gamma, tumor necrosis factor alpha, interleukins 2, 4 and 5, but not interleukin 10, are present in recurrent aphthous stomatitis. Arch Dermatol 1998;134:827-31.
23. MacPhail LA, Greenspan D, Feigal DW, Lennette ET, Greenspan JS. Recurrent aphthous ulcers in association with HIV infection: description of ulcer types and analysis of Tlymphocyte subsets. Oral Surg Oral Med Oral Pathol 1991;71:678-83.
24. Porter SR, Scully C. Orofacial manifestations in primary immunodeficiencies: common variable immunodeficiencies. J Oral Pathol Med 1993;22(4):157-8.
25. Flint SR, Sugerman P, Scully C, Smith JG, Smith MA. The myelodysplastic syndromes: case report and review. Oral Surg Oral Med Oral Pathol 1990;70:579-83.
26. Muzyka BC, Glick M. Major aphthous ulcers in patients with HIV disease. Oral Surg Oral Med Oral Pathol 1994;77(2):116-20.
27. MacPhail LA, Greenspan D, Feigal DW, Lennette ET, Greenspan JS. Recurrent aphthous ulcers in association with HIV infection. Description of ulcer types and analysis of Tlymphocyte subsets. Oral Surg Oral Med Oral Pathol 1991;71(6):678-83.
28. Miziara ID, Araujo Filho BC, Weber R. AIDS and Recurrent Aphthous Stomatitis. Rev Bras Otorrinolaringol (Engl Ed) 2005;71(4): 517-20.
29. Kerr AR, Ship JA. Management strategies for HIV-associated aphthous stomatitis. Am J Clin Dermatol. 2003;4(10):669-80.
30. Jacobson JM, Greenspan JS, Spritzler J, et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 1997;336(21): 1487-93.
31. Enwonwu CO. Noma, the ulcer of extreme poverty. N Engl J Med 2006;354(3):221-4.
32. Enwonwu CO, Falkler WA Jr, Phillips RS. Noma (cancrum oris). Lancet 2006;368 (9530): 147-56.
33. Veller-Fornasa C, Bezze G, Rosin S, Lazzaro M, Tarantello M, Cipriani R. Recurrent aphthous stomatitis and atopy. Acta Derm Venereol 2003;83(6):469-70.
34. Veller-Fornasa C, Gallina P. Recurrent aphthous stomatitis as an expression of pathergy in atopics. Acta Dermatovenerol Alp Panonica Adriat 2006;15(3):144-7.
35. Hsu PJ, Huang CJ, Wu MT. Pathergy in atypical eosinophilic pustular folliculitis. Int J Dermatol 2005;44(3):203-5.
36. Thomas HC, Ferguson A, McLennan JG, Mason DK. Food antibodies in oral disease. A study of serum antibodies to food proteins in aphthous ulceration and other oral disease. J Clin Pathol 1973:26:371-4.
37. Wray D, Vlagopoulos TP, Siraganian RP, Food allergens and basophil histamine release in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1982;54(4):388-95.
38. Hay KD, Reade PC. The use of an elimination diet in the treatment of recurrent aphthous ulceration of the oral cavity. Oral Surg Oral Med Oral Pathol 1984;57:504-7.
39. Nolan A, Lamey PJ, Milligan KA, Forsyth A. Recurrent aphthous ulceration and food sensitivity. J Oral Pathol Med 1991;20:473-5.
40. Hunter IP, Ferguson MM, Scully C, Galloway AR, Main ANH, Russell RI. Effects of dietary gluten elimination in patients with recurrent minor aphthous stomatitis and no detectable gluten enteropathy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1993;75: 595-8.
41. Tommasini A, Not T, Kiren V, et al. Mass screening for coeliac disease using antihuman transglutaminase antibody assay. Arch Dis Child 2004;89(6):512-5.
42. Aydemir S, Tekin NS, Aktunç E, Numanoglu G, Ustündag Y. Celiac disease in patients having recurrent aphthous stomatitis. Turk J Gastroenterol 2004;15(3):192-5.
43. Ross R, Kitscher AH, Zegarelli EV, et al. Relationship of mechanical trauma to recurrent aphthous stomatitis. NY State Dent J 1958;22:101-2.
44. Wray D, Graykowski EA, Notkins AL. Role of mucosal injury in initiating recurrent aphthous stomatitis. Br Med J 1981;283:1569-70.
45. Nazzaro P. Cutaneous manifestations of Behçet’s disease. In: Monacelli M, Nazzaro P (Eds). Behçet’s disaese. Basle 1966: Karger, 166:15-41.
46. Dellinger TM, Livingston HM. Aspirin burn of the oral cavity. Ann Pharmacotherapy 1998;32:1107.
47. McLeod RI. Drug-induced aphthous ulcers. Br J Dermatol 2000;143:1137-9.
48. Healy CM, Thornhill MH. An association between recurrent orogenital ulceration and non-steroidal anti-inflammatory drugs. J Oral Pathol Med 1995;24(1):46-8.
49. Lam PP. Severe stomatitis caused by penicillamine. Br Dent J 1980;149:180-1.
50. Bauer J, Fartasch M, Schuler G, Schell H. Ulcerative stomatitis as clinical clue to inadvertent methotrexate overdose. Hautarzt 1999;50:670-3.
51. Boulinguez S, Cornee-Leplat I, Bouyssou- Gauthier ML, Bedane C, Bonnetblanc JM. Analysis of the literature about drug-induced aphthous ulcers. Ann Dermatol Venereol 2000;127(2):155-8.
52. Hunter L, Addy M. Chlorhexidine gluconate mouthwash in the management of minor aphthous ulceration: a double-blind, placebocontrolled cross-over trial. Br Dent J 1987; 162:106-10.
53. Skaare AB, Herlofson BB, Barkvoll P. Mouthrinses containing triclosan reduce the incidence of recurrent aphthous ulcers (RAU). J Clin Periodontol 1996;23:778-81.
54. Meiller TF, Kutcher MJ, Overholser CD, Niehaus C, DePaola LG, Siegel MA. Effect of an antimicrobial mouthrinse on recurrent aphthous ulcerations. Oral Surg Oral Med Oral Pathol 1991;72:425-9.
55. Rattan J, Schneider M, Arber N, Gorsky M, Dayan D. Sucralfate suspension as a treatment of recurrent aphthous stomatitis. J Intern Med 1994;236(3):341-3.
56. Andriani E, Bugli T, Aalders M, et al. Efficacia e accettabilità di un dispositivo medico per le afte buccali. Minerva Pediatr 2000;52: 15-20.
57. Nolan A, Baillie C, Badminton J, Rudralingham M, Seymour RA. The efficacy of topical hyaluronic acid in the management of recurrent aphthous ulceration. J Oral Pathol Med 2006;35(8):461-5.
58. Mascaro JM, Lecha M, Torras H. Thalidomide in the treatment of recurrent necrotic and giant mucocutaneous aphtae and aphtosis. Arch Dermatol 1979;15:636-7.
59. de Wazières B, Gil H, Magy N, Berthier S, Vuitton DA, Dupond JL. Treatment of recurrent ulceration with low doses of thalidomide. Pilot study in 17 patients. Rev Med Intern 1999;20(7):567-70.
60. Altenburg A, Abdel-Naser MB, Seeber H, Abdallah M, Zouboulis CC. Practical aspects of management of recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol 2007;21 (8):1019-26.
61. Marshall GS, Edwards KM, Butler J, Lawton AR. Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. J Pediatr 1987; 110:43-6.
62. Pinto A, Rochelle G, Lindemeyer G, Thomas P. The PFAPA syndrome in oral medicine: differential diagnosis and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:35-9.
63. Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr 1999;135:15-21.
64. Feder HM Jr. Periodic fever, aphthous stomatitis, pharyngitis, adenitis: a clinical review of a new syndrome. Curr Opin Pediatr 2000; 12:253-6.
65. Tasher D, Somekh E, Dalal I. PFAPA syndrome: new clinical aspects disclosed. Arch Dis Child 2006 ;91(12):981-4.
66. Saulsbury FT, Wispelwey B. Tumor necrosis factor receptor-associated periodic syndrome in a young adult who had features of periodic fever, aphthous stomatitis, pharyngitis, and adenitis as a child. J Pediatr 2005;146 (2):283-5.
67. Ródenas JM, Ortego N, Herranz MT, Tercedor J, Pinar A, Quero JH. Cyclic neutropenia: a cause of recurrent aphthous stomatitis not to be missed. Dermatology 1992;184(3): 205-7.
68. Hammond WP 4th, Price TH, Souza LM, Dale DC. Treatment of cyclic neutropenia with granulocyte colony-stimulating factor. N Engl J Med 1989;320(20):1306-11.
69. Pipitone N, Boiardi L, Olivieri I, et al. Clinical manifestations of Behçet’s disease in 137 Italian patients: results of a multicenter study. Clin Exp Rheumatol 2004;22(6 Suppl 36):S46- 51.
70. Martini A. Behçet’s disease and Takayasu’s disease in children. Curr Opin Rheumatol 1995;7(5):449-54.
71. Zouboulis C, Kotter I, Djawari D, et al. Epidemiological features of Adamantiades- Behçet’s disease in Germany and in Europe. Yonsei Med J 1997;38:411-22.
72. Kim DK, Chang SN, Bang D, Lee ES, Lee S. Clinical analysis of 40 cases of childhoodonset Behçet’s disease. Pediatr Dermatol 1994;11(2):95-101.
73. Marchetti F, Trevisiol C, Ventura A. Intestinal involvement in children with Behçet’s disease. Lancet 2002;359(9323):2115.
74. Field EA, Allan RB. Review article: oral ulceration: aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic. Aliment Pharmacol Ther 2003;18:949-62.
75. Hyams JS. Extraintestinal manifestations of inflammatory bowel disease in children. J Pediatr Gastroenterol Nutr 1994;19(1):7-21.
76. Plauth M, Jenss H, Meyle J. Oral manifestations of Crohn’s disease: an analysis of 79 cases. J Clin Gastroenterol 1991;13(1):29-37.
77. Ventura A, Candusso M, Martelossi S, et al. Le molte facce della malattia infiammatoria cronica intestinale. Medico e Bambino 1998; 17(8):509-22.
78. Pittock S, Drumm B, Fleming P, et al. The oral cavity in Crohn’s disease. J Pediatr 2001; 138(5):767-71.
2. Porter SR, Scully C, Pedersen A. Recurrent aphthous stomatitis. Crit Rev Oral Biol Med 1998;9(3):306-21.
3. Scully C. Aphthous ulceration. N Engl J Med 2006;355:165-72.
4. Natah SS, Konttinen YT, Enattah NS, Ashammakhi N, Sharkey KA, Häyrinen-Immonen R. Recurrent aphthous ulcers today: a review of the growing knowledge. Int J Oral Maxillofac Surg 2004;33:221-34.
5. Rogers RS 3rd. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg 1997;16:278-83.
6. Cooke BED. Recurrent oral ulcers. Br J Dermatol 1969;81:159-61.
7. Lehner T. Autoimmunity in oral diseases, with special reference to recurrent oral ulceration. Proc R Soc Med 1968;61:515-24.
8. Pedersen A. Recurrent aphthous ulceration: Virological and immunological aspects. APMIS 1993;101(Suppl 37):37.
9. Martin DK, Nelms DC, Macler BF, Peavy DL. Lymphoproliferative responses induced by streptococcal antigens in recurrent aphthous stomatitis and Behçet’s syndrome. Clin Immunol Immunopathol 1979;13:1446-55.
10. Lindemann RA, Riviere GR, Sapp JP. Serum antibody responses to indigenous oral mucosal antigens and selected laboratorymaintained bacteria in recurrent aphthous ulceration. Oral Surg 1985;59:585-9.
11. Eglin RP, Lehner T, Subak-Sharpe JH. Detection of RNA complimentary to herpes simplex virus in mononuclear cells from patients with Behçet’s syndrome and recurrent oral ulcers. Lancet 1982;2:1356-61.
12. Studd M, McCance DJ, Lehner T. Detection of HSV-1 DNA in patients with Behçet’s syndrome and in patients with recurrent oral ulcers by the polymerase chain reaction. J Med Microbiol 1991;34:39-43.
13. Ship II. Epidemiologic aspects of recurrent aphthous ulcerations. Oral Surg Oral Med Oral Pathol 1972;33:400-6.
14. Miller MF, Ship II. A retrospective study of the prevalence and incidence of recurrent aphthous ulcers in a professional population, 1958-1971. Oral Surg Oral Med Oral Pathol 1977;43:532-7.
15. Ferguson MM, Wray D, Carmichael HA, Russell RI, Lee FD. Coeliac disease associated with recurrent aphthae. Gut 1980;21:223-6.
16. Freysdottir J, Lau S, Fortune F. Gammadelta T cells in Behçet’s disease (BD) and recurrent aphthous stomatitis (RAS). Clin Exp Immunol 1999;118:451-7.
17. Natah SS, Hayrinen-Immonen R, Hietanen J, Malmstrom M, Konttinen YT. Immunolocalization of tumor necrosis factor-alpha expressing cells in recurrent aphthous ulcer lesions (RAU). J Oral Pathol Med 2000;29(1):19-25.
18. Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med 1991; 173:699-703.
19. Pizarro A, Herranz P, de Lucas R, Borbujo J, Casado M. Pentoxifylline in recurrent aphthous stomatitis. J Am Acad Dermatol 1997; 36(2 Pt 1):284.
20. Sfikakis PP. Behçet’s disease: a new target for anti-tumour necrosis factor treatment. Ann Rheum Dis 2002 Nov;61 (Suppl 2):ii51-3.
21. Lewkowicz N, Lewkowicz P, Banasik M, Kurnatowska A, Tchorzewski H. Predominance of Type 1 cytokines and decreased number of CD4(+)CD25(+high) T regulatory cells in peripheral blood of patients with recurrent aphthous ulcerations. Immunol Lett 2005;99:57-62.
22. Buno IJ, Huff JC, Weston WL, Cook DT, Brice SL. Elevated levels of interferon gamma, tumor necrosis factor alpha, interleukins 2, 4 and 5, but not interleukin 10, are present in recurrent aphthous stomatitis. Arch Dermatol 1998;134:827-31.
23. MacPhail LA, Greenspan D, Feigal DW, Lennette ET, Greenspan JS. Recurrent aphthous ulcers in association with HIV infection: description of ulcer types and analysis of Tlymphocyte subsets. Oral Surg Oral Med Oral Pathol 1991;71:678-83.
24. Porter SR, Scully C. Orofacial manifestations in primary immunodeficiencies: common variable immunodeficiencies. J Oral Pathol Med 1993;22(4):157-8.
25. Flint SR, Sugerman P, Scully C, Smith JG, Smith MA. The myelodysplastic syndromes: case report and review. Oral Surg Oral Med Oral Pathol 1990;70:579-83.
26. Muzyka BC, Glick M. Major aphthous ulcers in patients with HIV disease. Oral Surg Oral Med Oral Pathol 1994;77(2):116-20.
27. MacPhail LA, Greenspan D, Feigal DW, Lennette ET, Greenspan JS. Recurrent aphthous ulcers in association with HIV infection. Description of ulcer types and analysis of Tlymphocyte subsets. Oral Surg Oral Med Oral Pathol 1991;71(6):678-83.
28. Miziara ID, Araujo Filho BC, Weber R. AIDS and Recurrent Aphthous Stomatitis. Rev Bras Otorrinolaringol (Engl Ed) 2005;71(4): 517-20.
29. Kerr AR, Ship JA. Management strategies for HIV-associated aphthous stomatitis. Am J Clin Dermatol. 2003;4(10):669-80.
30. Jacobson JM, Greenspan JS, Spritzler J, et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 1997;336(21): 1487-93.
31. Enwonwu CO. Noma, the ulcer of extreme poverty. N Engl J Med 2006;354(3):221-4.
32. Enwonwu CO, Falkler WA Jr, Phillips RS. Noma (cancrum oris). Lancet 2006;368 (9530): 147-56.
33. Veller-Fornasa C, Bezze G, Rosin S, Lazzaro M, Tarantello M, Cipriani R. Recurrent aphthous stomatitis and atopy. Acta Derm Venereol 2003;83(6):469-70.
34. Veller-Fornasa C, Gallina P. Recurrent aphthous stomatitis as an expression of pathergy in atopics. Acta Dermatovenerol Alp Panonica Adriat 2006;15(3):144-7.
35. Hsu PJ, Huang CJ, Wu MT. Pathergy in atypical eosinophilic pustular folliculitis. Int J Dermatol 2005;44(3):203-5.
36. Thomas HC, Ferguson A, McLennan JG, Mason DK. Food antibodies in oral disease. A study of serum antibodies to food proteins in aphthous ulceration and other oral disease. J Clin Pathol 1973:26:371-4.
37. Wray D, Vlagopoulos TP, Siraganian RP, Food allergens and basophil histamine release in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1982;54(4):388-95.
38. Hay KD, Reade PC. The use of an elimination diet in the treatment of recurrent aphthous ulceration of the oral cavity. Oral Surg Oral Med Oral Pathol 1984;57:504-7.
39. Nolan A, Lamey PJ, Milligan KA, Forsyth A. Recurrent aphthous ulceration and food sensitivity. J Oral Pathol Med 1991;20:473-5.
40. Hunter IP, Ferguson MM, Scully C, Galloway AR, Main ANH, Russell RI. Effects of dietary gluten elimination in patients with recurrent minor aphthous stomatitis and no detectable gluten enteropathy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1993;75: 595-8.
41. Tommasini A, Not T, Kiren V, et al. Mass screening for coeliac disease using antihuman transglutaminase antibody assay. Arch Dis Child 2004;89(6):512-5.
42. Aydemir S, Tekin NS, Aktunç E, Numanoglu G, Ustündag Y. Celiac disease in patients having recurrent aphthous stomatitis. Turk J Gastroenterol 2004;15(3):192-5.
43. Ross R, Kitscher AH, Zegarelli EV, et al. Relationship of mechanical trauma to recurrent aphthous stomatitis. NY State Dent J 1958;22:101-2.
44. Wray D, Graykowski EA, Notkins AL. Role of mucosal injury in initiating recurrent aphthous stomatitis. Br Med J 1981;283:1569-70.
45. Nazzaro P. Cutaneous manifestations of Behçet’s disease. In: Monacelli M, Nazzaro P (Eds). Behçet’s disaese. Basle 1966: Karger, 166:15-41.
46. Dellinger TM, Livingston HM. Aspirin burn of the oral cavity. Ann Pharmacotherapy 1998;32:1107.
47. McLeod RI. Drug-induced aphthous ulcers. Br J Dermatol 2000;143:1137-9.
48. Healy CM, Thornhill MH. An association between recurrent orogenital ulceration and non-steroidal anti-inflammatory drugs. J Oral Pathol Med 1995;24(1):46-8.
49. Lam PP. Severe stomatitis caused by penicillamine. Br Dent J 1980;149:180-1.
50. Bauer J, Fartasch M, Schuler G, Schell H. Ulcerative stomatitis as clinical clue to inadvertent methotrexate overdose. Hautarzt 1999;50:670-3.
51. Boulinguez S, Cornee-Leplat I, Bouyssou- Gauthier ML, Bedane C, Bonnetblanc JM. Analysis of the literature about drug-induced aphthous ulcers. Ann Dermatol Venereol 2000;127(2):155-8.
52. Hunter L, Addy M. Chlorhexidine gluconate mouthwash in the management of minor aphthous ulceration: a double-blind, placebocontrolled cross-over trial. Br Dent J 1987; 162:106-10.
53. Skaare AB, Herlofson BB, Barkvoll P. Mouthrinses containing triclosan reduce the incidence of recurrent aphthous ulcers (RAU). J Clin Periodontol 1996;23:778-81.
54. Meiller TF, Kutcher MJ, Overholser CD, Niehaus C, DePaola LG, Siegel MA. Effect of an antimicrobial mouthrinse on recurrent aphthous ulcerations. Oral Surg Oral Med Oral Pathol 1991;72:425-9.
55. Rattan J, Schneider M, Arber N, Gorsky M, Dayan D. Sucralfate suspension as a treatment of recurrent aphthous stomatitis. J Intern Med 1994;236(3):341-3.
56. Andriani E, Bugli T, Aalders M, et al. Efficacia e accettabilità di un dispositivo medico per le afte buccali. Minerva Pediatr 2000;52: 15-20.
57. Nolan A, Baillie C, Badminton J, Rudralingham M, Seymour RA. The efficacy of topical hyaluronic acid in the management of recurrent aphthous ulceration. J Oral Pathol Med 2006;35(8):461-5.
58. Mascaro JM, Lecha M, Torras H. Thalidomide in the treatment of recurrent necrotic and giant mucocutaneous aphtae and aphtosis. Arch Dermatol 1979;15:636-7.
59. de Wazières B, Gil H, Magy N, Berthier S, Vuitton DA, Dupond JL. Treatment of recurrent ulceration with low doses of thalidomide. Pilot study in 17 patients. Rev Med Intern 1999;20(7):567-70.
60. Altenburg A, Abdel-Naser MB, Seeber H, Abdallah M, Zouboulis CC. Practical aspects of management of recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol 2007;21 (8):1019-26.
61. Marshall GS, Edwards KM, Butler J, Lawton AR. Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. J Pediatr 1987; 110:43-6.
62. Pinto A, Rochelle G, Lindemeyer G, Thomas P. The PFAPA syndrome in oral medicine: differential diagnosis and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:35-9.
63. Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr 1999;135:15-21.
64. Feder HM Jr. Periodic fever, aphthous stomatitis, pharyngitis, adenitis: a clinical review of a new syndrome. Curr Opin Pediatr 2000; 12:253-6.
65. Tasher D, Somekh E, Dalal I. PFAPA syndrome: new clinical aspects disclosed. Arch Dis Child 2006 ;91(12):981-4.
66. Saulsbury FT, Wispelwey B. Tumor necrosis factor receptor-associated periodic syndrome in a young adult who had features of periodic fever, aphthous stomatitis, pharyngitis, and adenitis as a child. J Pediatr 2005;146 (2):283-5.
67. Ródenas JM, Ortego N, Herranz MT, Tercedor J, Pinar A, Quero JH. Cyclic neutropenia: a cause of recurrent aphthous stomatitis not to be missed. Dermatology 1992;184(3): 205-7.
68. Hammond WP 4th, Price TH, Souza LM, Dale DC. Treatment of cyclic neutropenia with granulocyte colony-stimulating factor. N Engl J Med 1989;320(20):1306-11.
69. Pipitone N, Boiardi L, Olivieri I, et al. Clinical manifestations of Behçet’s disease in 137 Italian patients: results of a multicenter study. Clin Exp Rheumatol 2004;22(6 Suppl 36):S46- 51.
70. Martini A. Behçet’s disease and Takayasu’s disease in children. Curr Opin Rheumatol 1995;7(5):449-54.
71. Zouboulis C, Kotter I, Djawari D, et al. Epidemiological features of Adamantiades- Behçet’s disease in Germany and in Europe. Yonsei Med J 1997;38:411-22.
72. Kim DK, Chang SN, Bang D, Lee ES, Lee S. Clinical analysis of 40 cases of childhoodonset Behçet’s disease. Pediatr Dermatol 1994;11(2):95-101.
73. Marchetti F, Trevisiol C, Ventura A. Intestinal involvement in children with Behçet’s disease. Lancet 2002;359(9323):2115.
74. Field EA, Allan RB. Review article: oral ulceration: aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic. Aliment Pharmacol Ther 2003;18:949-62.
75. Hyams JS. Extraintestinal manifestations of inflammatory bowel disease in children. J Pediatr Gastroenterol Nutr 1994;19(1):7-21.
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